[Ganoderma lucidum spore polysaccharides regulate JAK2/STAT3 pathway to alleviate cancer-related fatigue in mouse model of spleen deficiency syndrome].

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Citation abstract

Ganoderma lucidum spore polysaccharides(GLSP) are the main active ingredients of G. lucidum spores and have pharmacological effects of regulating immunity and inhibiting tumor growth. Cancer-related fatigue is a common concomitant symptom in cancer patients, with no safe and effective therapy. This study established a mouse model of cancer-related fatigue with spleen deficiency syndrome to investigate the effect and mechanism of GLSP in alleviating cancer-related fatigue. First, GLSP was obtained by water extraction and alcohol precipitation, and its content was measured to be approximately 75% by the anthrone sulfate method. GLSP was found to be composed of 10 monosaccharides including glucose, galactose, and mannose by 1-phenyl-3-methyl-5-pyrazolone(PMP) derivatization-HPLC. Using a mouse model of cancer-related fatigue due to spleen deficiency, this study showed that GLSP significantly reduced the tumor volume and weight, prolonged the running time, increased the motilin and gastrin content in the antral tissue, and improved the gastrointestinal digestive function in mice. Moreover, GLSP lowered the serum lactic acid level, increased the ATP concentration in the skeletal muscle, raised the levels of mitochondrial respiratory enzymes Ⅰ and Ⅳ, and promoted material and energy metabolism in the body. In addition, GLSP significantly alleviated the abnormal spleen tissue structure, promoted tumor tissue necrosis, lowered the serum levels of inflammatory factors [interleukin(IL)-1β, tumor necrosis factor(TNF)-α)], increased CD4~+ expression in the spleen tissue, reduced CD8~+ expression, and down-regulated the protein and mRNA levels of JAK2/STAT3 pathway-related factors in model mice. To sum up, GLSP can inhibit Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3) activation by reducing IL-6 expression, raise the CD4~+/CD8~+ level, regulate the tumor microenvironment, enhance immunity, improve gastrointestinal absorption and digestion, promote energy metabolism, and increase the skeletal muscle energy storage level, thereby relieving cancer-related fatigue in mice with the spleen deficiency syndrome.